| Benedict Cumberbatch | Sherlock Holmes |
| Martin Freeman | Dr. John Watson |
| Una Stubbs | Mrs. Hudson |
| Zoe Telford | Sarah |
| Louise Brealey | Molly Hooper |
| Gemma Chan | Soo Lin Yao |
| Al Weaver | Andy Galbraith |
| Bertie Carvel | Seb Wilkes |
| Daniel Percival | Eddie Van Coon
(as Dan Percival) |
| Paul Chequer | DI Dimmock |
| Howard Coggins | Brian Lukis |
| Janice Acquah | Museum Director |
| Jack Bence | Raz |
| John Macmillan | Community Officer |
| Olivia Poulet | Amanda |
| Jacqueline Chan | Shopkeeper
(as Jacqui Chan) |
| Sarah Lam | Opera Singer |
| Gillian Elisa | Surgery Receptionist |
| Stefan Pejic | Box Office Manager |
| Philip Starnier | German Tourist
(as Philip Benjamin) |
| Patrick Bradford | Additional
(uncredited) |
| Joanna Burnett | Tour Guide
(uncredited) |
| Claire Cage | Eddie's Neighbour
(uncredited) |
| Joe Hall | Homeless Guy
(uncredited) |
| Daniel van der Molen | Bank Worker
(uncredited) |