Background: Disturbance in cell cycle regulatory genes is a common finding among many types of cancers. The aim of this study is to evaluate the role of cyclin D1 and DJ-1 in benign prostatic hyperplasia (BPH) and prostate cancer (PC). Method: The current study enclosed 40 patients diagnosed with PC and 40 cases of BPH. The expression level of cyclin D1 and DJ-1 were evaluated by immunohistochemistry (IHC). Cyclin D1 scored depending on the percentage of stained nuclear tumor cells. While scoring of DJ-1 was based on intensity. The results were correlated with clinicopathological features and outcome. Results: In the PC group, cyclin D1 was detected in 95% and overexpressed in 42.5%, DJ-1 was positively stained in 85% and overexpressed in 47.5%. Meanwhile, in the BPH group, cyclin D1 was not detected and DJ-1 stained in only 2.5%. There was a statistically significant difference in Gleason score (GS), tumor stage, size, and treatment failure (p =< 0.001). In the terms of PC diagnosis prediction, although cyclin D1 was more specific (100%), DJ-1 is more sensitive than cyclin D1 (80%, 70%, respectively) (p = 0.000). Conclusions: Cyclin D1 and DJ-1 may emerge as a promising way for diagnosis of PC in certain circumstances, as the presence of insufficient tissue sampling,