Renal infarction is an underdiagnosed and underreported condition with multiple etiologies. A 45-year-old man presented with acute pain in the right lumbar region, CT scan showed a wedge shaped, non-enhancing, hypodense lesion in the cortex of the upper pole of the right kidney- suggestive of infarct. A pro-thrombotic workup revealed a protein S deficiency and a heterozygous mutation for MTHFR gene. Protein S is a vitamin-K dependent plasma glycoprotein, the deficiency of which is associated with a hypercoagulable state, which in turn led to renal infarction in this patient.