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There are currently few large-scale studies describing the clinical characteristics of these histological variants of prostate cancer (PCa) and the prognostic results of these patients. Thus, we used the Surveillance, Epidemiology, and End Results (SEER) database to achieve a more comprehensive understanding of the current prevalence and prognosis of these histological variants. A total of 780 (3.3%) patients with histological variants and 235834 patients with typical adenocarcinoma were included in the present study. The variants group presented with a more advanced stage than the typical adenocarcinoma group. The results also showed that patients with neuroendocrine (NE) PCa were more likely to have visceral metastases. In prognostic comparison, we found that variants, except for mucinous, had a worse prognosis than typical adenocarcinoma. Moreover, among these variants, we also discovered that NEPCa patients with low prostate-specific antigen level had the worst survival. In contrast, mucinous PCa had similar overall survival to typical adenocarcinoma. PATIENT SUMMARY: We reported follow-up results for prostate cancer (PCa) patients from the Surveillance, Epidemiology, and End Results database (2004-2016). We focused on the prognosis of PCa with different histological variants and evaluated the risk factors that were significant in predicting poor prognosis. We suggested that neuroendocrine PCa patients should receive active treatment as soon as possible to improve their prognosis. We still need further studies to identify the role of mucinous PCa in patients' prognosis compared with typical adenocarcinoma.