While there are dozens of tissue clearing techniques described in the literature, there are few that have been demonstrated for use with 3D cell culture models. Additionally, most of these tissue clearing techniques are not designed for compatibility with well plates (e.g. iDISCO, BABB, uDISCO, 3DISCO) or high-throughput processing (e.g. CLARITY) and many are not compatible with immunofluorescent labeling (ScaleS4, CUBIC) or have high toxicity (e.g. ClearT). Therefore, we developed the Visikol HISTO-M tissue clearing technique to be rapid, easy-to-use, plate compatibility, fluorescent protein compatible and immunofluorescence compatible.