Two cases of Waldenstrom's macroglobulinemia (WM) that occurred in employees from one university academic department were investigated using approaches for both cluster and single case investigation. Common personal characteristics and potential past hazardous exposures were evaluated. The patients shared a young age at diagnosis, worked in the same building, and had similar duration of time between first entering the building and diagnosis of WM. No evidence was found to support the original hypothesis that exposure to radioactive material could be related to the occurrence of WM. Although this investigation did not identify a common causal agent among two cases of a rare disease, investigations of disease clusters may be useful for developing etiologic hypotheses even when a full-scale epidemiologic study is not undertaken. Detailed descriptions of case characteristics can help generate ideas for further research.