This study investigates the role of tumor-associated ALOX5+ mast cells (MCs) in cervical cancer (CC) progression using single-cell RNA sequencing. The researchers analyzed single-cell data from ten CC tumor samples, identifying 1392 MCs subdivided into seven subpopulations. Notably, the C2 subpopulation, characterized by ALOX5 expression, showed close associations with tumor-related MCs and was at a critical stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. Functional experiments in HeLa and CaSki cell lines confirmed that downregulating the TNFRSF12A gene partially inhibited CC development. A prognostic model based on the marker genes of the C2 subpopulation was constructed, demonstrating excellent predictive value for patient prognosis. These findings provide new insights into the complex interactions between MCs and the tumor microenvironment in CC, offering potential therapeutic targets and improved clinical decision-making.This study investigates the role of tumor-associated ALOX5+ mast cells (MCs) in cervical cancer (CC) progression using single-cell RNA sequencing. The researchers analyzed single-cell data from ten CC tumor samples, identifying 1392 MCs subdivided into seven subpopulations. Notably, the C2 subpopulation, characterized by ALOX5 expression, showed close associations with tumor-related MCs and was at a critical stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. Functional experiments in HeLa and CaSki cell lines confirmed that downregulating the TNFRSF12A gene partially inhibited CC development. A prognostic model based on the marker genes of the C2 subpopulation was constructed, demonstrating excellent predictive value for patient prognosis. These findings provide new insights into the complex interactions between MCs and the tumor microenvironment in CC, offering potential therapeutic targets and improved clinical decision-making.