A biopsy device includes a cutter defining a cutter lumen and a tissue sample holder for collecting tissue samples. In one example, the tissue sample holder has a rotatable manifold that is configured to redirect fluid from one axial direction to an opposite axial direction. The tissue sample holder also has a plurality of tissue sample trays through which fluid may be communicated. The tissue sample trays define chambers that are each configured to separately hold tissue samples. The tissue sample trays are removable relative to the manifold. A cup is configured to cover the manifold and trays. A tissue sample holder rotation mechanism is operable to rotate the manifold to successively index each chamber of the tissue sample trays with the cutter lumen. A feature may prevent rotation of the manifold when one part of the biopsy device is separated from another part of the biopsy device.