Holmes's building at 63rd street and Wallace was called by neighbors the "castle" of Englewood. It was a large, strange, dismal building with a basement, a sub-basement, a kiln, a room-sized vault lined in iron, a gas line that connected to the vault for no apparent reason except to pump in gas, and halls that veered off at odd angles. In the cellars, investigators found pits filled with ashes and quicklime, a substance that quickly dissolves human corpses.

Holmes had a pharmacy business on the ground floor and rented space to other businesses and residents. The third floor contained hotel rooms, while the second floor had 35 unique, strange rooms. Some of these rooms were windowless and fitted with air-tight doors.

When investigators entered the basement, they found a hidden chamber with piles of quicklime, an acid vat with human ribs and a skull inside, and a dissection table. They also found other bones: ribs from a child, vertebrae, a foot bone, a shoulder blade, and a hip socket. They found clothing, bloodstained overalls, surgical equipment, and vats of quicklime and ash. In yet another hidden room in the basement, they found human skeletons including one from a little girl.

Holmes would quickly burn the building down. However, it was clear that he often gassed his victims in the upstairs rooms or the vault and then brought the corpses to the basement rooms.