Androgen receptor (AR) and kallikrein (KLK-2) regulates the PSA (prostate specific antigen) transcription and activation, respectively. We investigated the individual and combined risk of KLK-2, PSA and AR gene polymorphism in histologically confirmed CaP patients and healthy controls from north India. DNA was extracted from peripheral blood leucocytes pellet of 277 subjects. AR repeats analysis was done by PCR-Genscan method. PSA and KLK-2 were genotyped by PCR-RFLP method. Kruskal-Wallis test and logistic regression was applied for mean comparison and risk determination. A significant association for CaP risk was observed with short AR-CAG repeats (OR=3.36, p<0.001) and CC genotype of KLK-2 (OR=2.78, p=0.031), however, no association was found with PSA and AR-GGN repeat polymorphism. PSA/GG genotype was significantly associated with higher Gleason score (> or =7) of tumor (OR=6.23, p<0.01). No association was observed with other confounding variables such as PSA and age with any of these polymorphisms. Thus, we hypothesize that these polymorphisms may influence the etiology of CaP and may have the probability to become appropriate marker either independently or in combination. The combined information on serum PSA level, PSA (G/A), KLK-2 (C/T) genotypes and AR (CAG; GGN repeat) may assist in the deterrence of unnecessary biopsies.