The importance of the complete absence of a hemidiaphragm or unilateral diaphragmatic agenesis in adulthood in relation to performing laparoscopic procedures has not been well documented. This article reports for the first time in literature a case of successful laparoscopic cholecystectomy in an adult with previously undiagnosed unilateral diaphragmatic agenesis. A 36-year-old female complaining of stubborn right upper abdominal pain radiating to her upper back was diagnosed as having cholelithiasis and was scheduled for laparoscopic cholecystectomy. There were also bilateral upper extremity malformations to a certain level. Routine diagnostic tests demonstrated that her entire liver and some bowel loops were in the right hemithorax, suggesting right-sided diaphragmatic hernia. Laparoscopic procedure was performed with the insertion of four trocars. Exploration of abdomen revealed total absence of the right hemidiaphragm. Cholecystectomy was completed laparoscopically in about 45 minutes without need for additional trocars. Patient had an uneventful recovery and was discharged on the second postoperative day without any complaint. Laparoscopic cholecystectomy in adults with diaphragmatic agenesis and intrathoracic abdominal viscera can be performed successfully. Nevertheless, any bile duct aberrations must be documented prior to surgery, and the surgeon should be able to convert to open procedure if necessary.