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Marylebone is in an area of London that can be roughly defined as bounded by Oxford Street to the south, Marylebone Road to the north, Edgware Road to the west and Great Portland Street to the east. A broader definition designates the historic area as Marylebone Village and encompasses neighbouring Regent's Park, Baker Street and the area immediately north of Marylebone Road, containing Marylebone Station, the original site of the Marylebone Cricket Club at Dorset Square, and the neighbourhood known as Lisson Grove to the border with St John's Wood. The area east of Great Portland Street up to Cleveland Street, known as Fitzrovia since the 1940s, is considered historically to be East Marylebone.

Today the area is host to many medical and dental offices, traditionally concentrated in Harley Street.