Differential diagnosis of cutaneous lymphoproliferative disorders represents one of the most vexing problems in dermatology and dermatopathology. Immunohistochemical and molecular techniques developed during the last 3 decades have added new criteria for the differentiation of these diseases. In this review, the main criteria for differential diagnosis of lymphoproliferative disorders of the skin, with special emphasis on immunohistochemical features detectable in routinely fixed paraffin-embedded tissue sections, are summarized. When classifying cutaneous lymphoproliferative disorders, it is crucial to remember that a correct diagnosis can only be reached when clinical data is integrated with histopathologic, immunohistochemical, and molecular features.