Huntington’s disease (HD) is a genetic neurological disorder characterized by early degeneration of enkephalin-expressing striatal neurons, also known as Medium-sized Spiny Neurons (MSNs). Therefore, accurate immunodetection of enkephalin expressing cells is of wide interest for the scientific community. Here, we describe an immunohistochemical procedure for the detection of the unprocessed precursor of the opioid peptide met-enkephalin, namely the preproenkephalin (Penk1), in mouse brain cryosections. The specificity of the immunolabeling has been confirmed by crossing a reporter mouse line whereby EYFP expression is obtained upon Cre-mediated recombination in animals carrying Cre recombinase under the control of the preproenkephalin promoter.