PURPOSE: The aim of this study was to report a case of fungal keratitis with subsequent corneal perforation after corneal collagen cross-linking (CXL) treatment performed for keratoconus. CASE REPORT: A 20-year-old woman presented with redness and discharge in the left eye. She had a history of bilateral CXL procedure performed for keratoconus elsewhere 4 days earlier. The visual acuity was hand motion in the left eye. Slit-lamp examination revealed extended corneal melting with surrounding infiltrates. The patient was hospitalized, and corneal epithelial scraping samples were sent for microbiological assessment. In the meantime, empirical antibiotic therapy (fortified topical antibiotics: vancomycin 50 mg/mL, ceftazidime 50 mg/mL, and fluconazole 2 mg/mL q1 hour) was initiated. In direct microscopy of the corneal scraping, septate hyaline fungal hyphae were detected and topical fluconazole was switched to topical voriconazole (10 mg/mL). Three days after hospitalization, corneal melting progressed to perforation and corneal suturing with 10-0 monofilament was performed to reform the anterior chamber. Complete resolution of keratitis with residual scarring was noticed in 2 weeks. Three months later, penetrating keratoplasty was performed to obtain better visual acuity. CONCLUSIONS: CXL with riboflavin has become a common procedure to prevent keratoconus progression by strengthening the biomechanical specialties of the cornea. Although the treatment itself has been used in the management of microbial keratitis and related corneal melting, fungal keratitis and corneal perforation after a CXL procedure for keratoconus might also be detected. Clinicians should be aware of this rare but devastating complication of CXL treatment and start prompt treatment when suspected.