Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.