We describe 2 patients with pigmented villonodular synovitis. In both patients, synovial fluids (SF) were characterized by the presence of abundant, strongly birefringent lipid microspherules, which appeared as Maltese crosses and were found both inside foam cells and free in the SF. Histologically, the synovial membranes showed pigmented villonodular synovitis, with aggregation of foam cells containing abundant lipid microspherules in their cytoplasm. Observation of numerous birefringent lipid microspherules and foam cells in SF may be a clue to the diagnosis of pigmented villonodular synovitis.