INTRODUCTION: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are immune-mediated liver diseases with female predominance. Combined features of both, termed AIH-PBC overlap syndrome, occurs in rare instances. We present a unique case of AIH-PBC overlap syndrome in twin males. CASE DESCRIPTION/METHODS: Twin #1 was a 36-year-old man when he presented in 2012 with asymptomatic liver enzyme elevation. No new medications, herbals, alcohol or illicit drug use. No known family history of liver disease. Labs showed total bilirubin (TB) 0.5, alkaline phosphatase (ALP) 478, aspartate aminotransferase (AST) 81, alanine aminotransferase (ALT) 111, gamma-glutamyl transferase (GGT) 625, positive anti-mitochondrial antibody (AMA) >1:640, and hypergammaglobulinemia (2128 mg/dL). Liver biopsy showed moderate plasma rich cell infiltrate with bile duct damage and mild fibrosis, consistent with AIH-PBC overlap. Patient was treated with steroids, azathioprine (AZA), and ursodeoxycholic acid (UDCA), later switched to obeticholic acid due to refractory PBC. He subsequently experienced marked biochemical improvement without disease progression. Twin #2 presented in 2017 with elevated liver enzymes and pruritus. Labs showed TB 1.1, ALP 755, AST 81, ALT 116, GGT 838, positive ANA >1:2560, positive AMA >100, and positive ASMA >100. Liver biopsy showed moderate bile duct epithelial injury with lymphoplasmacytic infiltrate, consistent with AIH-PBC overlap, and stage II/IV hepatic fibrosis. He was treated with steroids, AZA, and UDCA. He also experienced marked biochemical improvement without disease progression. DISCUSSION: PBC, a rare autoimmune disorder with female preponderance, can lead to cirrhosis and liver failure. PBC-AIH overlap syndrome, described in 4.8-9.2% patients with PBC, is more likely to have rapid disease progression and hepatic decompensation. Combination of steroids, AZA and UDCA has been variably effective and can delay disease progression. To the best of our knowledge, this is the first case of AIH-PBC overlap syndrome reported in twin males and highlights the importance of inherited factors in immune mediated liver disorders. Although it is known that PBC and AIH are associated with human leukocyte antigen genes on chromosome 6, further study of the association between these disorders is limited by the paucity of patients. Early diagnosis of this condition is essential to prevent liver related complications with medical management.