Acute mechanical intestinal obstruction is one of the most common modes of presentation in patients with Peutz-Jeghers syndrome (PJS). This report presents a case of PJS with malignant acute jejunal obstruction accompanied by synchronous foci of duodenal, jejunal, and ileal cancer originated from hamartomatous polyps. The follow-up endoscopic findings of the patient also revealed severe polyposis of the entire gastrointestinal tract, including the stomach and colon, in addition to the small intestine. Very few cases of multifocal synchronous small intestinal cancer in PJS patients have been reported in the previous literature.