Background: Immunocompromised individuals, particularly those with AIDS, are at increased risk of developing lymphoproliferative tumours and opportunistic infections. Radiologic findings alone may not always distinguish between these entities. Case presentation: We describe the case of a patient with acquired immunodeficiency syndrome (AIDS) with rapidly worsening dyspnoea and clinical signs suggestive of acute respiratory distress syndrome (ARDS). Despite initial concerns for ARDS, autopsy revealed an advanced-stage, aggressive lymphoma as the underlying cause. This case highlights the challenge of differentiating ARDS from lymphoma in AIDS patients, especially when atypical radiologic findings, such as nodular opacities, are present. Conclusions: The diagnosis of ARDS relies on imaging, oxygenation abnormalities, and clinical timing. However, various infectious and non-infectious conditions can mimic ARDS, making an accurate differential diagnosis essential. This case adds to the literature by underscoring the importance of considering lymphoproliferative disorders in AIDS patients presenting with respiratory distress, especially in the absence of typical lymphoma-related symptoms.