The USS Sherlock Holmes (NCC-221B) was a Federation starship operated by Starfleet.

In 2364, the commanding officer was Captain Jeffery Joal Annon. That year, prior to stardate 41603.7, this ship, along with the USS Unicorn, received an order from Admiral Gregory Quinn of Starfleet Operational Support Services. Later that year, this order was read by Lieutenant Commander Data during an investigation into an alleged conspiracy in the highest levels of Starfleet Command. (TNG: "Conspiracy" okudagram)

The ship might have been named after the famed fictional detective, Sherlock Holmes. The registry was an in-joke as it was the house number of Holmes' residence on 221B Baker Street.
The star chart seen on this mission order could be seen on the mission order for the USS Endeavour. This chart was first seen in "Heart of Glory" aboard the Talarian freighter Batris. It was seen again in "Symbiosis" aboard the Ornaran freighter Sanction.
On several display graphics displaying the registry of the USS Enterprise-D, the second dash was omitted, with the registry written as NCC-1701D. If this was the case with the Sherlock Holmes, that would presumably make this the third starship to bear the name.

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