The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.