Hypertrophic osteoarthropathy (HOA) is a paraneoplastic syndrome consisting of digital clubbing, polyarthralgias, and periostosis that sometimes accompanies primary bronchogenic carcinoma and other pulmonary malignancies. We report a case of HOA as the initial manifestation of pulmonary metastases in a 42-year-old woman with malignant phyllodes tumor of the breast. Since the treatment for malignancy-associated HOA is targeted at the underlying neoplasm, it is important to make the diagnosis in a timely fashion so that appropriate therapy may be initiated without delay. HOA symptoms generally improve, as they did in our patient, if the cancer responds to treatment. The pathophysiology of HOA is poorly understood, but a role for tumor-associated humoral mediators has been postulated. The hypothesized mechanisms underlying HOA are reviewed, and evidence for a prominent role for platelet-derived growth factor in mediating this syndrome is examined. This unusual case illustrates the importance of suspecting HOA in a patient with a history of cancer who presents with otherwise unexplained polyarthralgias.