This study reported here was undertaken to determine the probability of malignancy in patients presenting with unexplained lymphadenopathy in primary care practice and to estimate the effectiveness of current referral patterns by family physicians in relation to malignant disease. Clinical characteristics that may be discriminatory for malignant causes were also investigated. A retrospective analysis was performed of 82 patients who underwent biopsy for unexplained lymphadenopathy from 1982 to 1984; data regarding the incidence of unexplained lymphadenopathy and the referral rate for this problem were obtained from registration projects. A total of 29 malignant lymphadenopathies were identified for a prior probability of 1.1 percent and a posterior (after referral) probability of 11 percent. The ability of the family physician to refer malignant cases within four weeks after initial consultation (sensitivity of referral) was 80 to 90 percent; 91 to 98 percent of benign cases were not referred (specificity of referral). An increased likelihood of malignancy was associated with age over 40 years (4 percent) and supraclavicular lymphadenopathy (50 percent). The incidence of malignancy in patients presenting with unexplained lymphadenopathy to the family physicians is very low (1 to 2 percent). Nevertheless, despite the paucity of validated discriminatory factors, the family physicians perform a reasonably effective selection process toward referral and biopsy.