Hyderabad is the third largest city of Pakistan, the second largest city of Sindh Province and one of the oldest cities of the sub-continent. This administrative headquarter is located just east of the River Indus and is an important commercial and industrial center. Once a provincial capital, it is at a distance of approximately 200-km from Karachi. This present study was conducted with the objective of providing the cancer profile of Hyderabad, which has an urban population of 2,840,653 (52.2% M, 47.8% F) annual growth rate 1.13. The city is inhabited by all ethnicities of the country, however the predominant ethnicity is Sindhi, followed by Mohajirs (post-partition immigrants from India), and a lesser extent other ethnicities of Pakistan viz. Baluchs, Punjabis and Pathans. The study includes two sets of patients. First the incident cancer cases, residents of Hyderabad, who reached Karachi for diagnosis or treatment. Second the incident cancer cases registered at the Aga Khan University Pathologybased Cancer Registry (APCR) Pathology collection points at Hyderabad and subsequently registered at APCR, during 1st January 1998 to 31st December 2002. The pathology department of the AKU has 3 centers in Hyderabad, which provide diagnostic pathology especially oncopathology services to the city. The age-standardized rates (ASR) for cancer (all sites) 1998 to 2002 in Hyderabad were 91.6/100,000 in males and 96.0/100,000 in females. The most common malignancies (ASR per 100,000) in males were oral cavity (11.8), lymphoma (10.6), lung (8.0), urinary bladder (6.8), prostate (4.8), liver (4.4), pharynx (4.2), colo-rectum (3.6), larynx (3.2), and skin (3.2). The cancers in females (ASR per 100,000) were breast (22.4), oral cavity (11.5), gall bladder (4.8), esophagus (4.2), cervix (3.6), ovary (3.4), colo-rectum (3.4), lymphoma (3.4), uterus (3.4), and thyroid (2.4). Tobacco-associated cancers were responsible for approximately 40.0% of the tumors in males and 20.0% in females. Histological confirmation remained 96.3%, with 44.5% presenting in grade II or I, 55.5% presenting as stage III and IV. Information on grade and stage of malignancy was available in 70% and 50% of the cases respectively. Males comprised 53.1%, and females 46.9% of the cases. The mean age of cancer all sites, both genders was 45.2 years (95% CI 44.4; 45.9), males 45.4 years (95% CI 44.3; 46.5); females 44.9 years (95% CI 43.9; 45.9). Conclusions drawn from this database must be interpreted with care, as it may be identified as data from selected medical institutions. Chances of selective collection bias are minimized as the data of the AKU pathology is collected from multiple centers in the city of Hyderabad, dispersed at distances, which allows adequate sampling from the entire city. There is a slight preponderance of lymphomas in males which we feel is a true higher risk, yet it may indicate an over representation of easily accessible sites in pathology based-data. Nonetheless, this is the first attempt to determine the cancer incidence pattern of Hyderabad, and should serve as a guideline for estimation of the cancer burden and risk assessment statistics of Pakistan and the cancer control program of the country.