Tuberculosis (TB) is a multidimensional disease, and interactions between individuals and groups are of extreme importance in its development. The aim of this study was to estimate the occurrence of pulmonary TB (PTB) to identify potential risk factors and to define high-risk areas in Portugal (2004-2006). The relevance of the common risk factors identified was evaluated at the national and local levels. Considering local public health at the municipality level, the main objective of this study was the support of local interventions, identifying local high-risk areas and the corresponding local risk factors. A complex statistical methodology based on correlation analysis, spatial clustering, risk maps and multivariate regression models was developed. The results showed that some areas were at higher risk of PTB than others due to high incidence of HIV/AIDS, incarceration, nonstandard (abnormal) and/or crowded accommodation, unemployment and immigrant populations. The majority of these areas showed increased TB incidence rates.