Background: Retinoids have the capacity to accelerate the involution ofmultiple keratoacanthomas, including unusual variants such as keratoacanthoma marginatum centrifugum and keratoacanthoma en plaque that may persist and be associated with progressive growth and provide difficulties in diagnosis and management. Observations: We describe 3 patients who had unusual infiltrated and keratotic plaques affecting the lower legs or nasolabial area that persisted or recurred that may be related to this group of unusual keratoacanthomas. The 3 patients had differing clinical lesions that did not resemble classic keratoacanthomas, but were linked by their biopsy findings of hypertrophic lichen planus-like reaction and pseudoepitheliomatous hyperplasia with a prominent infundibulocystic component that progressed to multiple keratoacanthomas or infundibulocystic squamous cell carcinoma. Polymerase chain reaction analysis of biopsy material from 2 patients failed to detect human papillomavirus. All 3 presentations provided a therapeutic dilemma, but responded rapidly to acitretin treatment at a dosage of 10 to 25 mg daily, which was continued for 15 to 24 months. Conclusions: These cases illustrate an unusual reaction pattern that is hypertrophic lichen planus-like but, instead of evolving to classic lichen planus, progresses to infundibulocystic hyperplasia and the development of multiple keratoacanthomas or infundibulocystic squamous cell carcinomas. Retinoids represent a therapeutic option for this difficult clinical problem and may obviate repeated and extensive surgery. Background: Retinoids have the capacity to accelerate the involution of multiple keratoacanthomas, including unusual variants such as keratoacanthoma marginatum centrifugum and keratoacanthoma en plaque that may persist and be associated with progressive growth and provide difficulties in diagnosis and management. Observations: We describe 3 patients who had unusual infiltrated and keratotic plaques affecting the lower legs or nasolabial area that persisted or recurred that may be related to this group of unusual keratoacanthomas. The 3 patients had differing clinical lesions that did not resemble classic keratoacanthomas, but were linked by their biopsy findings of hypertrophic lichen planus-like reaction and pseudoepitheliomatous hyperplasia with a prominent infundibulocystic component that progressed to multiple keratoacanthomas or infundibulocystic squamous cell carcinoma. Polymerase chain reaction analysis of biopsy material from 2 patients failed to detect human papillomavirus. Al l 3 presentations provided a therapeutic dilemma, but rapidly to acitretin treatment at a dosage of 10 to 25 mg daily, which was continued for 15 to 24 months. Conclusions: These cases illustrate an unusual reaction pattern that is hypertrophic lichen planus-like but , instead of evolving to classic lichen planus, progresses to infundibulocystic hyperplasia and the development of multiple keratoacanthomas or infundibulocystic squamous cell carcinomas. Retinoids represent a therapeutic option for this problem difficult clinical problem and may obviate repeated and extensive surgery.