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Keloids and hypertrophic scars occur in 30–90% of patients. The two conditions have different clinical and histochemical characteristics and, unfortunately, still represent a great challenge for clinicians due to the lack of effective treatments. Current advances are revealing new preventive and therapeutic options that offer hope for managing this widespread, chronic, and debilitating problem. Case report: We report on the efficacy of the combination of fractionated carbon dioxide (FCO2) laser and intra-lesional 5-fluorouracil (5-FU) for the treatment of a mid-thoracic keloid scar resistant to intra-lesional infiltration steroids and pressotherapy. Discussion: The appearance of cortisone dermatitis at the site of corticosteroid infiltration makes it necessary to seek an effective therapeutic alternative to minimize the risk of recurrence and resistance. The possibility of combining several therapeutic means, such as laser, 5-FU, or Bleomycin and cryosurgery, should be readily explored. Conclusion: Further efforts are needed to select the treatment with maximum results. Combination therapy appears to be an acceptable method for the treatment of keloids.