Prostate cancer is the most frequent cancer among men in most developed countries, yet little is known about its causes. Older age, Asian ancestry and a positive family history of prostate cancer have long been recognized as important risk factors. The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion, mosaic and Drug metabolizing gene polymorphism (CYP, GST) in prostate cancer patients of Tamilnadu, Southern India. Totally 62 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by using fluorescence in situ hybridization (FISH). Fluorescence in situ hybridization (FISH) has used to identify the target genes for some of these chromosomal alterations. Our results showed frequent CA in chromosomes X. By conventional cytogenetics, predominant changes included gain of chromosome, loss of Y, deletions of 7q and l0q, and the appearance of double minutes. We found major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). We determined the genotypic frequency of the GSTM1 null, GSTT1 null and to understand whether the GST polymorphisms are associated with the risk of sporadic prostate cancer in South India. In the present study, individuals with the CYP1A1 Val alleles appeared to be more susceptible in terms of Prostrate Cancer, with the CYP1A1 Val/Val genotype in particular increasing the risk. In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the prostate cancer tumorigenesis. Identification of CA may be helpful in understanding the molecular basis of the disease.