A 46-year-old woman and a 39-year-old male, both of African origin, consulted the general practitioner because of back pain and blurry vision, respectively. After several months of diagnostic delay, the woman was diagnosed with a diffuse large B-cell lymphoma and the man with progressive multifocal leukoencephalopathy, each secondary to a chronic HIV infection. In retrospect, both patients' medical histories and physical examinations had revealed signs and symptoms of an HIV infection. Since the prevalence of HIV is high in many African countries, one should be highly suspicious of possible infection with HIV, even when a patient presents with everyday complaints; patients originating from high-risk areas in particular should be tested for HIV. Careful history-taking and a thorough physical examination can be helpful in collecting diagnostic clues pointing towards HIV.