With an incidence of 1 in 60,000 to 300,000 individuals in the United States, Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder. PJS is defined by gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation, and an increased risk of malignancies. The occurrence of polyps in the GI system may cause chronic bleeding resulting in anemia, and/or obstructions that result in the telescoping of a section of the bowel into an adjacent section. Individuals with PJS have an 80% to 90% lifetime risk of cancer such as colorectal, gastric, pancreatic, breast, and ovarian cancers. The disorder causes significant mortality and morbidity as a consequence of the size and location of intestinal polyps, and the occurrence and location of malignancies. PJS is associated with sequence variants in the serine/threonine kinase 11 (STK11) gene, which encodes the LKB1 kinase protein. PJS is managed mainly through treatment of the manifestations of the disorder. Surveillance of the GI tract for detection of polyps and screening for several cancer types is recommended, especially stomach, small and large bowel, and breast cancers.