Peritoneal mesothelioma is a malignant mesothelioma that forms in the peritoneum, the portion of the mesothelium that surrounds the stomach and the intestines in the abdominal cavity. The exact cause of peritoneal mesothelioma is something of a mystery. It is well-established that asbestos exposure is the proximate cause of peritoneal mesothelioma, but unlike in pleural mesothelioma where the means by which the asbestos fibers cause the disease is well understood, medical researchers are divided about what is happening in peritoneal mesothelioma. The principal question is how the asbestos fibers are getting into the peritoneum, since it is not connected directly to the lungs. Some researchers believe that peritoneal mesothelioma is caused when asbestos fibers are ingested in water or (more rarely) food, and then migrate through the stomach or intestinal wall. Other researchers believe that the asbestos fibers must be coming in through the lungs and then migrating into the peritoneum via the lymph system or the bloodstream. It is even possible that asbestos fibers might be present in sputum which is coughed up and then ingested.

Peritoneal mesothelioma follows a similar progression as pleural mesothelioma, but obviously affects different portions of the body. Rather than compressing the lung, the peritoneal mesothelioma tumor expands into the bowel or creates a distended stomach, and the excess fluid that is produced by the tumor goes into the abdominal cavity rather than flowing in the pleura. Between 20 and 35 percent of cases of malignant mesothelioma are peritoneal. It is possible for peritoneal mesothelioma to spread back into the pleura and for a patient to develop both pleural and peritoneal mesothelioma; this seems to happen more frequently from the peritoneum to the pleura, rather than the other way around.

Peritoneal mesothelioma differs from pleural mesothelioma because it attacks a different portion of the body. The symptoms of peritoneal mesothelioma often do not become serious until the disease has progressed significantly. Symptoms include abdominal pain, palpable masses in the abdomen, bowel function problems, weight loss, and a buildup of fluid in the abdomen known as ascites. In order to diagnosis peritoneal mesothelioma, the doctor will begin with a cytological test, examining abdominal fluid under a microscope to look for cancer cells. Further diagnostic work involves a biopsy conducted via laparoscopy, but further diagnostic surgery (i.e. a conventional biopsy) may be required as laparoscopic examination does not always produce enough testable tissue.

There is an extremely rare form of peritoneal mesothelioma in which the testicles of a male patient develop tumors. The covering of the scrotum is actually an outgrowth of the peritoneal mesothelium. It is believed that fibers from the stomach may migrate to the scrotal covering and that a typical mesothelioma can form there. This is exceptionally rare, however.