Introduction: This study was conducted to assess the patterns of primary central nervous system (CNS) malignancies in Karachi South (KS), a moderate risk population in Asia. Materials and Methods: Data for 321 registered cases were reviewed and analyzed in two periods 1995-1997 (111 cases, 75 (67.6%) male (M); 36 (32.4%) female (F)) and 1998-2002 (210 cases, 124 (59.1%) M; 86 (40.9%) F). Results: Age standardized incidence rate per 100,000, crude incidence rate and relative frequency in 1995-1997 were 3.5, 2.8 and 3.5% (M) and 1.8, 1.6 and 1.7% (F). Corresponding figures for 1998-2002 were 3.3, 2.7 and 2.7% (M) and 3.3, 2.7 and 2.1% (F). Mean age of male and female patients during 1995-1997 was 33.3 years (SD± 20.4) and 30.7 years (SD±19.6). Mean ages for 1998-2002 were 33.2 years (SD±19.5) and 28.7 years (SD±18.5) for males and females respectively. In males, 199 malignancies were reported, 106 (86.9%) cases in the brain, 10 (5.5%) in meninges and 12 (6.0%) in the spinal cord; 122 cases were observed in females, 177 (89%) cases in the brain, 8 (6.6%) each in the meninges and spinal cord. The most common morphology was astrocytoma (72 (36.2%) (M); 40 (32.7%) (F)). Mean age of low grade astrocytoma was 27.8 years (M) and 27.0 years (F); anaplastic astrocytomas, 40.5 years (M), 34.1 years (F) and glioblastoma, 45.7 years (M) and 38.3 years (F). Youngest cases were registered for cerebellum and brain stem. Conclusion: The incidence of CNS malignancies is stable in males and gradually increasing in females. Astrocytoma is the commonest morphology; they affect a younger age group and show an age gradient in proportion to tumor grade. The mean age varied by sub-site and histology. Focus should be directed towards the understanding the biological nature and risk factors prevalent in this population.