On December 10, 2010, about 1720 central standard time, a Beech 300, N206K, received substantial damage during an in-flight door separation after departure from Minneapolis-St Paul International/Wold-Chamberlain Airport (MSP), Minneapolis, Minnesota. The airplane returned and landed at MSP without further incident. Visual meteorological conditions prevailed at the time accident. The airline transport pilot and one passenger were uninjured. The 14 Code of Federal Regulations Part 91 flight was operating on an instrument rules flight plan. The flight originated from MSP about 1718 and was en route to Joe Foss Field Airport (FSD), Sioux Falls, South Dakota. According to the Federal Aviation Administration (FAA), the airplane was climbing through 7,000 feet when the pilot reported to Minneapolis Air Traffic Control that the airplane had a pressurization problem. He did not report that the cabin entry door had separated from the airplane. Examination of the airplane by the FAA revealed an estimated 4-inch hole in the rear fuselage and no damage to the fuselage cabin entry door pin holes. Electrical continuity of the door wiring was confirmed, and the door open annunciator light was functional. On January 26, 2011, the door was located about 6 miles west of MSP. The door handle was in the latch position and not in the lock position. No mechanical anomalies were noted with the door.