The Italian cancer registries network has not been sufficiently developed in the Southern regions. General practitioners (GPs) are knowledgeable about the prevalence, incidence and mortality for different types of cancer in their patient populations. The aim of this pilot study was to verify the feasibility and reliability of the characterization of cancer populations using GP databases in order to evaluate the impact of cancer in the general population of Naples. The characteristics of the cases studied have been collected by interview or electronic health record and recorded on paper or magnetic supports, appropriately conforming to the current privacy law. Databases are centralized, stored and codified on electronic data-sheets and periodically elaborated by the ‘Consorzio Nazionale delle Cooperative Mediche’ and ‘Federico II’ University. The present study was initiated on September 15, 2004. The analysed geographical area included the suburbs of ‘Stella’ and ‘San Carlo all’Arena’, situated in the historical center of Naples and corresponding to Health Care District 29 of the local health service. The analysis included 16,927 men and women (age range, 6–97 years) from the outpatient offices of 12 GPs who agreed to participate in the study. Results showed that the analysed population represents 16.3% of the general population residing in the area under study. We identified 342 (2%) patients with cancer, 143 (0.8%) of whom were men and 199 (1.2%) women (M/F ratio of 0.7). Of the 342 patients, 10 (5 men and 5 women) had a double cancer; thus, a total of 352 malignancies was characterized. Cancer prevalence was 2,020/100,000 inhabitants. This estimate is lower compared to the national prevalence (2,683/100,000 inhabitants) but higher compared to that in other southern Italian areas. Results, stratified by International Classification of Disease, ninth revision (ICD-IX), based on factors including gender and age, demonstrated that breast cancer, urogenital tumours and colorectal cancer are the most frequently occurring types of cancer identified among the inhabitants of Naples. Cancer prevalence in the historical center of Naples is in concordance with national estimates and projections and National Cancer Registries may be easily and accurately supported by GP medical databases.