Papillary lesions of the breast represent a heterogeneous group with differing biological behaviour. Correct diagnosis is crucial but maybe difficult, as many benign and malignant papillary lesions have similar appearances. Immunohistochemistry plays a useful role in their differentiation. Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. In intracystic papillary carcinoma, there is controversy as to the presence of complete myoepithelial cell layer around these lesions. p63 is the marker of choice as the staining is nuclear, cross reactivity is minimal, and sensitivity is high. Papilloma may frequently be complicated by superimposed different types of epithelial hyperplasia, which range from usual to atypical or even ductal carcinoma in situ, and they many be morphologically similar. Basal cytokeratins are useful to differentiate these entities; as usual hyperplasia is positive for basal cytokeratins with a mosaic staining pattern. CK5/6 is probably the best marker. Neuroendocrine markers (chromogranin A and synaptophysin) may be positive in papillary carcinoma, particularly in the solid type, and there may be some overlap with the ductal carcinoma in situ with spindle cells or endocrine ductal carcinoma in situ. A panel of CK5/6, p63 and neuroendocrine markers can be useful in the diagnostic work up of problematic papillary lesions of the breast. As the experience with these markers is still rather limited, it is too early to recommend basing treatment choices on these marker studies alone. Complete removal of lesion is probably still the treatment of choice.