Hereditary papillary renal cell carcinoma (HPRCC) is an autosomal dominant syndrome characterized by the occurrence of bilateral and multifocal, classic type papillary renal cell carcinomas. In the recent decades, extensive molecular studies have narrowed the molecular underpinnings of this syndrome to missense mutations in tyrosine kinase domain of MET proto-oncogene. Although MET mutations are specific to HPRCC, it has been found in sporadic papillary renal cell carcinomas and as recently reported, in biphasic squamoid alveolar variant of papillary renal cell carcinoma. Dual MET/VEGFR2 kinase inhibitor and tyrosine kinase inhibitors have shown promising results in systemic therapy for HPRCC.