Infections with Entamoeba histolytica are seen worldwide and are more prevalent in the tropics. About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes, ranging from dysentery to abscesses of the liver or other organs. Extra-intestinal infection by E. histolytica most often involves liver. Pleuro-pulmonary involvement, seen as the second most common extra-intestinal pattern of infection, is frequently associated with amebic liver abscess. Pulmonary amebiasis occurs in about 2-3% of patients with invasive amebiasis. We report herein the case of a 45-year-old male presenting with hepato-pulmonary amebiasis. The diagnosis was established from direct examination of sputum, in which trophozoites of E. histolytica were detected, and by serology. Following treatment with metronidazole and chloroquine, the clinical evolution improved significantly. On regular follow-up visits, the patient was asymptomatic. This case report reiterates the need for collaboration between clinicians and microbiologists for timely diagnosis of such infections.