Here we demonstrate a screen using patient-derived 3D spheroids (tumoroids) where—in addition to readouts on cell viability—we adapted the Cell Painting assay for the 3D tumor model. Tumoroids were formed from primary cells isolated from a patient-derived tumor explant that represents metaplastic breast cancer with a triple-negative breast cancer. Results demonstrate the feasibility of using the Cell Painting assay on 3D cell models.