Tertiary lymphoid structures (TLSs) are ectopic lymphoid organs that develop in non-lymphoid tissues at sites of chronic inflammation, including tumours. TLSs have key characteristics similar to secondary lymphoid organogenesis. TLSs exist in different maturation states in tumours, culminating in germinal centre formation. The mechanisms underlying the role of TLSs in the adaptive antitumour immune response are being deciphered. The correlation between TLS presence and clinical benefit in patients with cancer suggests that TLSs could be a prognostic and predictive factor. A major challenge is to exploit TLSs to promote lymphocyte infiltration, activation by tumour antigens and differentiation to increase the antitumour immune response. Several approaches are being developed using chemokines, cytokines, antibodies, antigen-presenting cells or synthetic scaffolds to induce TLS formation. Strategies aiming to induce TLS neogenesis in immune-low tumours and in immune-high tumours, in combination with therapeutic agents dampening the inflammatory environment and/or with immune checkpoint inhibitors, represent promising avenues for cancer treatment. Cancer development is a multistep process involving accumulation of genetic modifications responsible for unregulated cell division, survival and death. Accumulation of genetic mutations results in the expression of tumour antigens that trigger innate and adaptive antitumour immune responses to eliminate cancer cells. The description of tumour-infiltrating lymphocytes (TILs) with effector and memory functions within primary tumours and their metastases and the discovery of the correlation between the density of CD8+ T effector memory cells at the site of the primary tumour and the survival of patients unambiguously demonstrated the importance of the tumour microenvironment (TME) in cancer control. Classically, the generation of an efficient adaptive immune response against cancer occurs in secondary lymphoid organs (SLOs), wherein major histocompatibility complex (MHC) molecule–peptide complexes are presented to CD4+ T and CD8+ T cells by mature dendritic cells (DCs), and requires the migration of DCs from the tumour site to the SLOs. B cells are activated in the SLOs upon antigen binding in primary follicles and receive help from the CD4+ T cells to proliferate and form a secondary follicle that progressively becomes a germinal centre. These steps allow lymphocyte proliferation and differentiation into effector T (Teff) cells and B memory cells that migrate into the tumour and lead to the destruction of tumour cells. However, studies on the TME revealed further insight into the generation and regulation of the antitumour defences by showing that they occur not only in SLOs but also directly at the tumour site within organized cellular aggregates resembling SLOs called tertiary lymphoid structures (TLSs). TLSs reflect lymphoid neogenesis occurring in peripheral tissues upon long-lasting exposure to inflammatory signals mediated by chemokines andTertiary lymphoid structures (TLSs) are ectopic lymphoid organs that develop in non-lymphoid tissues at sites of chronic inflammation, including tumours. TLSs have key characteristics similar to secondary lymphoid organogenesis. TLSs exist in different maturation states in tumours, culminating in germinal centre formation. The mechanisms underlying the role of TLSs in the adaptive antitumour immune response are being deciphered. The correlation between TLS presence and clinical benefit in patients with cancer suggests that TLSs could be a prognostic and predictive factor. A major challenge is to exploit TLSs to promote lymphocyte infiltration, activation by tumour antigens and differentiation to increase the antitumour immune response. Several approaches are being developed using chemokines, cytokines, antibodies, antigen-presenting cells or synthetic scaffolds to induce TLS formation. Strategies aiming to induce TLS neogenesis in immune-low tumours and in immune-high tumours, in combination with therapeutic agents dampening the inflammatory environment and/or with immune checkpoint inhibitors, represent promising avenues for cancer treatment. Cancer development is a multistep process involving accumulation of genetic modifications responsible for unregulated cell division, survival and death. Accumulation of genetic mutations results in the expression of tumour antigens that trigger innate and adaptive antitumour immune responses to eliminate cancer cells. The description of tumour-infiltrating lymphocytes (TILs) with effector and memory functions within primary tumours and their metastases and the discovery of the correlation between the density of CD8+ T effector memory cells at the site of the primary tumour and the survival of patients unambiguously demonstrated the importance of the tumour microenvironment (TME) in cancer control. Classically, the generation of an efficient adaptive immune response against cancer occurs in secondary lymphoid organs (SLOs), wherein major histocompatibility complex (MHC) molecule–peptide complexes are presented to CD4+ T and CD8+ T cells by mature dendritic cells (DCs), and requires the migration of DCs from the tumour site to the SLOs. B cells are activated in the SLOs upon antigen binding in primary follicles and receive help from the CD4+ T cells to proliferate and form a secondary follicle that progressively becomes a germinal centre. These steps allow lymphocyte proliferation and differentiation into effector T (Teff) cells and B memory cells that migrate into the tumour and lead to the destruction of tumour cells. However, studies on the TME revealed further insight into the generation and regulation of the antitumour defences by showing that they occur not only in SLOs but also directly at the tumour site within organized cellular aggregates resembling SLOs called tertiary lymphoid structures (TLSs). TLSs reflect lymphoid neogenesis occurring in peripheral tissues upon long-lasting exposure to inflammatory signals mediated by chemokines and