The Dr. Job Holmes House is house at 527 Main Street in Calais, Maine. It was built in 1850 by Dr. Job Holmes, a prominent local physician, and is a fine local example of Italianate architecture. It is now owned by the St. Croix Historic Society, along with Holmes' first house, the Holmes Cottage next door, which is operated as Dr. Job Holmes Cottage & Museum. Dr. Job Holmes House was listed on the National Register of Historic Places in 1990.