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A 35-year-old male presented with corneal ulceration on the left eye with a history of treatment over several months. At the first visit in our department we saw an elliptically shaped ulcerative stromal keratitis with circular peripheral neovascularization. There was organized hypopyon with hyphemia. The best corrected visual acuity (BCVA) was light perception. The patient had used contact lenses for many years. Under the suspicion of herpetic keratitis due to a positive "dendrite" the patient had undergone antiviral therapy for 6 months in a different department. Our diagnosis was Acanthamoeba keratitis. We performed penetrating excimer laser keratoplasty-à-chaud (8.0 × 7.0 mm/8.1 × 7.1 mm) with simultaneous cryotherapy of the mid-peripheral cornea. The topical therapy was polyhexamethylene biguanide, propamidine isoethionate, neomycin and steroids in intervals. A repeat penetrating excimer laser keratoplasty (8.5 × 7.5 mm/8.6 × 7.6 mm) with simultaneous amniotic membrane patch and lateral tarsorrhaphy was performed 2 months later due to melting of the graft with positive Seidel test. After successful surgery of the mature cataract the BCVA was 20/25. In a patient with a positive contact lens history acanthamoeba keratitis should always be considered as a differential diagnosis to herpes simplex keratitis in the early course of the disease.