The aim of the present study was to differentiate between prostate adenocarcinoma and urothelial carcinoma among Egyptian patients by immunohistochemical methods. Two groups of patients were used: urothelial group, consisted of 9 cystitis, 21 transitional cell carcinoma (TCC) and 5 urinary bladder mucoid adenocarcinoma (MAC) and prostatic group, consisted of 9 nodular prostatic hyperplasia (NPH) and 21 prostatic adenocarcinoma (PAC). H–E stained sections were performed to confirm the diagnosis and evaluate the histopathological characteristics of the tumor. Immunohistochemical techniques were used for detection of P63, CK7, CK10 and PSA. The results showed that in urothelial group, positive p63and CK7 immunostaining was observed in all cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma. All cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma were CK10 and PSA negative. In prostate group, positive p63 immunostaining was observed in all cases of NPH and in prostatic adenocarcinoma. Positive CK7 immunostaining was observed in all cases of NPH while all cases of prostatic adenocarcinoma were CK7 negative. Positive CK10 immunostaining was observed in all cases of NPH. In prostatic adenocarcinoma, 11 cases were CK10 positive and 10 cases were CK10 negative. All cases of NPH and prostatic adenocarcinoma were PSA positive. In conclusion, the result of the present work proved that p63 and CK7 can be used along with other markers to differentiate between adenocarcinoma of prostate and urothelial carcinoma of the bladder. Also, CK10 and PSA are useful for distinguishing prostate cancer from urothelial carcinoma.