In a retrospective study the clinical course of 40 patients with symptomatic persistent or recurrent parathyroid cancer was analyzed in order to assess the value of aggressive surgical intervention. Recurrence was diagnosed after a median period of 33 months (1-228 months). Twenty-two patients had locoregional disease, whereas 14 patients had both local and distant spread. The remaining four patients had distant spread. Patients with just locoregional disease were subject to one to nine reoperative procedures. The median survival time from the last operation was 39 months (1-204 months). Eight patients then had no evidence of disease, three were hypercalcemic and 9 of 11 had died of parathyroid cancer. Distant spread was demonstrated in 17 of 40 patients. Pulmonary metastases predominated (14 of 17). Surgical excision was performed in 9 of 14 cases. Of these nine, two patients had a subsequent disease-free interval of 36+ and 72+ months, respectively. One patient was reported hypercalcemic after 84 months, whereas five patients died of cancer between 4 and 60 months after their last surgical exploration. One patient was lost to follow-up. In all, 21 patients (53%) died of parathyroid cancer. Conspicuous nuclear atypia and frequent mitoses predominated. Image cytometric DNA analysis showed high rates for all three groups (median p90 = 80%, range 21-98%).