Using Medline, Embase, and the Science Citation Index, we summarize the cutaneous adverse effects of transdermal and parenteral fentanyl. The fentanyl transdermal therapeutic system (TTS; patch) provides continuous systemic delivery of fentanyl (N-phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide), a potent opioid analgesic, for 72 hours. Clinical studies of fentanyl TTSs demonstrated varying rates of irritation at the application site, ranging from none to 42%, with a median of 25%. Most descriptions of skin reactions included erythema at the application site, indicating irritant dermatitis. Skin testing in 2 subjects receiving parenteral doses concluded that although immunoglobulin E (IgE) antibodies to fentanyl exist, few cases of immediate-type allergic reactions to fentanyl have been substantiated. Comparing the reactions to anesthetic agents during allergenic testing demonstrated positive "wheal and flare" to fentanyl in only 1 of 50 patients (2%). Pruritus has been frequently reported during administration of epidural fentanyl, but allergenicity has not been shown. The few case reports of possible anaphylactic reactions to fentanyl have not clearly demonstrated fentanyl as the causal agent. In addition, transdermal and intravenous/epidural routes of administration may not be comparable because of large differences in plasma concentrations: When these results are taken together, fentanyl (TTS) has shown limited skin intolerance.