Spherical cancer models are three-dimensional (3D) in vitro models used in cancer research to mimic the in vivo tumor environment. These models include multicellular tumor spheroids (MCTS), tumorospheres, tissue-derived tumor spheres (TDTS), and organotypic multicellular spheroids (OMS). Each model has distinct characteristics and applications in cancer research, particularly in studying chemoresistance, radioresistance, tumorigenicity, and invasion and migration. MCTS are formed from single-cell suspensions in nonadherent conditions and are characterized by their well-rounded shape and ability to maintain as free-floating cultures. Tumorospheres are models of cancer stem cell (CSC) expansion, developed in serum-free medium with growth factors. TDTS are formed by partial dissociation of tumor tissue and maintain cell-cell contact. OMS are generated by cutting tumor tissue and are closely resembling in vivo tumors. These models are valuable for studying cancer biology, as they provide a more accurate representation of the tumor microenvironment compared to traditional 2D cultures. They allow for the study of drug sensitivity and resistance, as well as the behavior of CSCs. However, the terminology used to describe these models can be confusing, and careful classification is necessary to ensure their appropriate application. The MCTS model has been widely used to study tumor biology, including radioresistance and chemosensitivity. Tumorospheres are particularly useful for studying CSCs and their role in tumor recurrence. TDTS and OMS provide insights into tumor heterogeneity and the behavior of tumor cells in a 3D environment. These models are essential for understanding cancer progression and for developing more effective therapies.Spherical cancer models are three-dimensional (3D) in vitro models used in cancer research to mimic the in vivo tumor environment. These models include multicellular tumor spheroids (MCTS), tumorospheres, tissue-derived tumor spheres (TDTS), and organotypic multicellular spheroids (OMS). Each model has distinct characteristics and applications in cancer research, particularly in studying chemoresistance, radioresistance, tumorigenicity, and invasion and migration. MCTS are formed from single-cell suspensions in nonadherent conditions and are characterized by their well-rounded shape and ability to maintain as free-floating cultures. Tumorospheres are models of cancer stem cell (CSC) expansion, developed in serum-free medium with growth factors. TDTS are formed by partial dissociation of tumor tissue and maintain cell-cell contact. OMS are generated by cutting tumor tissue and are closely resembling in vivo tumors. These models are valuable for studying cancer biology, as they provide a more accurate representation of the tumor microenvironment compared to traditional 2D cultures. They allow for the study of drug sensitivity and resistance, as well as the behavior of CSCs. However, the terminology used to describe these models can be confusing, and careful classification is necessary to ensure their appropriate application. The MCTS model has been widely used to study tumor biology, including radioresistance and chemosensitivity. Tumorospheres are particularly useful for studying CSCs and their role in tumor recurrence. TDTS and OMS provide insights into tumor heterogeneity and the behavior of tumor cells in a 3D environment. These models are essential for understanding cancer progression and for developing more effective therapies.