Retrospective immunohistochemical and flow cytometric DNA analyses were performed on 56 cases of transitional cell carcinoma (TCC) to examine the biologic implications of epidermal growth factor receptor (EGFR) expression. A total of 28 (50%) cases were reactive for EGFR immunostaining. The receptor expression increased from 41.7 to 56.3% with tumor stage. There was a significant association between EGFR expression and tumor stage (p < 0.0005), but not tumor grade. The flow DNA content and the Ki-67 proliferating index had no relation to the status of EGFR (p = 1, respectively). For those receptor-positive tumors (n = 28), there was a significant association (p < 0.0001) between receptor expression and tumor proliferation. Interestingly, the DNA content was not correlated with EGFR expression (p = 0.69). We support the possible role of EGFR in cell proliferation and the potential significance for tumor growth in TCCs. However, the biology of TCC in half the cases could not be explained by this mechanism. The interaction between EGFR and DNA ploidy status necessitates further evaluation.