Tumor growth is associated with multiple changes at the gene expression level. Recognition of the genes differentially expressed between the cellular populations at various degrees of malignancy may provide valuable clues towards the identification of clinically useful diagnostic markers and/or therapeutic targets. In the present study, we used suppression subtractive PCR to identify differentially expressed genes with possible relevance for control of tumorigenic potential using two cervical carcinoma cell lines of the common HeLa origin, but of different capacity to generate tumors in nude mice. Screening of the subtracted libraries resulted in isolation of several known as well as novel genes including the gene encoding S100P calcium-binding protein that belongs to S100 family, whose members can bind and modulate effector proteins in a calcium-dependent manner. Expression of S100P was further studied in the context of different culture conditions and was found to correlate with the tumorigenic phenotype of the somatic cell hybrids between HeLa and normal human fibroblasts. Moreover, S100P was highly expressed in a number of tumorigenic cell lines derived from colorectal and breast carcinoma, suggesting that it is not restricted to a particular tumor type. Functional involvement of S100P in tumor growth was evaluated using tumor xenografts produced from the cells transfected with the full-length S100P cDNA. The results showed that S100P can positively affect anchorage-independent growth of the transfected cells and improve tumor formation in nude mice, suggesting that it actively participates in the control of the tumorigenic potential in vivo.