p204 overexpression in retinoblastoma (Rb)−/− mouse embryo fibroblasts or transfection of p204 mutated at both Rb‐binding sites confer growth advantages, resulting in a significantly higher number of foci in a cell focus assay. To investigate the possibility that mutated p204 acquires malignant transformation capability, NIH3T3 cells were stably transfected with the expression vector pRcRSV204 double‐mutant (p204dm) harboring both the C‐terminal deletion up to amino acid 568 and the point mutation from glutamic acid to lysine at position 427, and analyzed for markers typical of cell immortalization and transformation. We detected a greater abundance of cell colonies in soft agar with p204dm‐expressing cells than vector control cells. The p204dm‐transfected cells also displayed two other characteristics associated with malignant transformation, i.e. growth under low‐serum conditions and formation of tumors in athymic nude mice. Moreover, their telomerase activity was significantly higher than in the vector control cells. It would thus seem that p204, devoid of functional Rb‐binding motifs, can become oncogenic.