Unilateral malignant pleural effusion as an initial manifestation that leads to the diagnosis of an underlying acute lymphoblastic leukemia is a rare event. Early and accurate diagnosis of this case is important for prompt and adequate therapy. We present the case of an18-year-old male who presented to the emergency department with severe respiratory distress. Chest X-ray revealed a unilateral massive right-sided pleural effusion. Cytological examination of the pleural fluid led to the diagnosis of underlying acute lymphoblastic leukemia. Subsequent hemogram, bone marrow aspirate and flow cytometry analysis confirmed the diagnosis of T-lineage acute lymphoblastic leukemia. The patient underwent induction chemotherapy which led to significant clinical improvement due to resolution of the pleural effusion. The patient is on follow up at present. This case report exemplifies and highlights the importance of cytopathological analysis of body cavity fluids in the diagnosis of underlying unsuspected malignancies.