OBJECTIVE To investigate the expression of p16, retinoblastoma (pRb), and cyclin D1 oncoproteins in endometriomas and adenomyosis. METHODS Immunohistochemical study for p16, pRb, and cyclin D1 proteins in formalin-fixed paraffin-embedded endometriotic and adenomyotic tissues. METHODS University hospital. METHODS Tissues from 25 women with endometriomas and 31 women with adenomyosis were evaluated. METHODS Tissue samples were collected during gynecologic surgery and confirmed by histology to have endometriosis or adenomyosis. Nuclear expression of p16, pRb, and cyclin D1 proteins was examined by immunohistochemistry. METHODS Distribution and intensity of immunostaining. RESULTS In the proliferative phase of the cycle, p16 was detected in 77% of adenomyosis tissues but in only 15% of endometriosis tissues. Moreover, in adenomyosis samples positive for p16, 100% of the adenomyotic cells expressed p16, whereas only 10%-20% of endometriosis cells from positive cases expressed p16. In contrast, pRb was detected in 28% of endometriosis cases but not in any adenomyotic tissues. Cyclin D1 was absent in both endometriotic and adenomyotic tissue samples. CONCLUSIONS Differences in oncoprotein expression between endometriotic and adenomyotic tissues provide further evidence that the pathogenesis of endometriosis is different from that of adenomyosis.