Cytomegalovirus (CMV) pneumonia is a rare opportunistic infection in the setting of HIV (Human Immunodeficiency Virus)-infection. Establishing accurate diagnosis of CMV pneumonia in HIV-infection can be challenging. Co-infections by multiple opportunistic pathogens are common and a high degree of clinical vigilance to evaluate for multiple infections, including CMV pneumonia, should be maintained. As there can be a degree of overlap in clinical and radiological features amongst different opportunistic infections affecting the lungs, definitive microbiological and cytohistologic evidences are needed. Reliance on microbiological evidence of CMV in respiratory specimens alone for the diagnosis of CMV pneumonia will lead to an over-diagnosis of the condition and unnecessary treatment. In our case report, we describe a 53-year-old man with recently diagnosed HIV-infection who presented with non-resolving pneumonia. A diagnosis of CMV pneumonia was reached through consistent clinical, radiological, microbiological and cytologic investigations. The patient made a full clinical recovery after being started on anti-CMV treatment.