A protocol has been developed to investigate and report perceived clusters of cancer using a population-based cancer registry. The protocol comprises a series of steps which lead to assessment of the cluster's importance on the basis of three criteria: (1) statistical evidence of clustering; (2) documentation of the existence of exposure to a carcinogen; and (3) biological plausibility of the relationship between the exposure and the cancer of interest. The evaluation of these criteria results in one of three recommendations: further study, surveillance only, or no action. The protocol provides a systematic approach for investigation, makes efficient use of available cancer registry data, and responds to public concerns. The protocol is demonstrated by its application to an inquiry concerning an apparent excess of lung cancer in a small Ontario town and the possible role of radon gas exposure. The public health importance and limitations of addressing perceived disease clusters are discussed.