This study aimed to investigate the expression of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE)/caspase-8 inhibitory protein (c-FLIP) in endometrial carcinoma and its possible implications. c-FLIP protein was detected in 42 endometrial carcinoma tissues and in 22 normal proliferative endometrial tissues by immunohistochemistry. In addition, c-FLIP messenger ribonucleic acid (mRNA) was evaluated in 20 endometrial carcinomas and in 18 normal proliferative endometria by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using SYBR Green I(TM). The relationship between c-FLIP protein level and tumor cell proliferation and that between c-FLIP protein level and clinicopathologic parameters of patients with endometrial carcinoma was analyzed. c-FLIP protein expression was significantly higher in neoplastic tissues than in normal tissues (P < 0.01), and similar result was obtained from RT-PCR analysis of c-FLIP mRNA (P < 0.01). Furthermore, c-FLIP protein was significantly associated with proliferating cell nuclear antigen-labeling index (P < 0.01), clinical stage (P < 0.05), the presence of invasion to > 1/2 myometrium (P < 0.05), and lymph node metastasis (P < 0.01). Multivariate analysis of variance also confirmed the association of c-FLIP with clinical stage (P < 0.05) and with lymph node metastasis (P < 0.05), while its association with myometrial invasion was marginal (P = 0.059). It is concluded that c-FLIP might contribute to the carcinogenesis and aggressiveness of endometrial carcinoma and might be a useful prognostic factor in the tumor.