The homozygous methylenetetrahydrofolate reductase (MTHFR) gene mutation, which causes hyperhomocysteinemia, has been implicated in various thrombotic disorders [3]. While both conditions individually predispose to thrombosis, their coexistence is very rare and poses a significant additive thrombotic risk. This report details a case of acute pulmonary thromboembolism in a young male with the unusual combination of APS and a heterozygous MTHFR mutation, emphasizing the importance of a comprehensive hypercoagulability workup in unexplained thrombotic events. Here, MTHFR is linked to thrombotic disease.