Objective:To describe the recalled medical history, clinical manifestations, and treatment of yaws and syphilis by syphilis seroreactive blood donors in Kumasi, Ghana. Methods: Of the blood donors at Komfo Anokye Teaching Hospital, Kumasi, Ghana tested with the syphilis rapid diagnostic test (RDT) and later by rapid plasma reagin (RPR) test, 526 were seroreactive. Four hundred and seventy-one (89.5%) of these subjects were confirmed with the Ortho-Vitros Syphilis TP test as the gold standard and were interviewed to determine past or present clinical manifestations of yaws and syphilis. Results: Of the 471 respondent donors, 28 (5.9%) gave a history of skin lesions and sores; four (14.3%) of these subjects, who were all male and RPR-positive, recalled a diagnosis of syphilis. All four reported having had skin lesions/bumps with slow-healing sores, but only one of them had had these symptoms before the age of 15 years. Conclusions: A small proportion of confirmed seroreactive donors in this sample had any recall of symptoms or treatment for yaws or syphilis. These data suggest that clinical questioning adds little further information to the current screening algorithm. The relative contribution of yaws and syphilis to frequent positive tests in endemic areas remains speculative.