IL-17RC (interleukin-17 receptor-like) gene codes for a transmembrane protein, the full length of which inhibits apoptosis in prostate cancer cells. IL-17RC gene transcribes over a dozen different splice variants of mRNA. However, it is not known whether there are relevant protein isoforms. Here we report that different IL-17RC protein isoforms were detected by two different antibodies. The isoform as detected byanti-IL-17RC intracellular domain antibodies (anti-ICD) was expressed at higher levels in androgen-independent prostate cancer cell lines (PC3 and DU145) than in androgen-dependent prostatic cell lines (RWPE-1, pRNS-1-1, MLC-SV40, and LNCaP). In contrast, several isoforms as detected by anti-IL-17RC extracellular domain antibodies (anti-ECD) were expressed at significantly higher levels in androgen-dependent prostatic cell lines than in androgen-independent ones. Furthermore, immunohistochemical staining of prostate tissue microarrays showed that IL-17RC protein expression was significantly higher in androgen-independent prostate cancers than in androgen-dependent ones when anti-ICD was used, whereas the trend was reversed using anti-ECD. These observations provide evidence that IL-17RC protein isoforms are differentially expressed in prostatic cells and cancer tissues and may play a negative or positive role in the initiation and progression of prostate cancer.