•Pneumocystis jirovecii pneumonia is a main issue in non-HIV immunocompromised hosts.•HRCT is a crucial tool for guiding diagnosis in the appropriate clinical scenario.•Pneumocystis jirovecii pneumonia has a wide spectrum of mimickers at HRCT.•Clinical and laboratory findings are an essential support for the HRCT diagnosis. Pneumocystis jirovecii pneumonia (PJP) has emerged as a main issue in non Human Immunodeficiency Virus (HIV) immunocompromised hosts, exposing patients to high mortality rates, especially when the diagnosis is delayed. Since microbiological confirmation is often unfeasible or difficult to obtain, High-resolution Computed Tomography (HRCT) represents a main tool for guiding the diagnosis in the appropriate clinical scenario. Nevertheless, radiologists must be aware that PJP at HRCT is a multifaceted process, with a variety of common and less frequent findings, along with a broad spectrum of infectious (e.g., viral and certain fungal and bacterial pneumonias) and non-infectious (e.g., pulmonary oedema, diffuse alveolar haemorrhage, and drug toxicity) differential diagnoses. In this review we resume background clinical information on PJP in non-HIV immunocompromised patients, illustrate both typical and less frequent HRCT findings, and present the spectrum of infectious and non-infectious mimickers at HRCT, highlighting the similarities with PJP and providing clues for the differential diagnosis.