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Patients with Barrett's esophagus are at risk for dysplasia and esophageal adenocarcinoma. Although surgery was the mainstay treatment for Barrett's dysplasia and cancer, patients with high-grade dysplasia and early cancers now have several nonsurgical treatment options. Most of the endoscopic therapies are relatively safe but do carry a risk for complications. Treatment failure with progression of the disease is the most severe complication, especially among patients with low surgical risk. Cryoablation has been used with promising results in both high-grade dysplasia and early esophageal cancer. A patient with a well-documented history of Barrett's esophagus with high-grade dysplasia that underwent multiple sessions of photodynamic therapy and salvage cryoablation for residual high-grade dysplasia was presented. The patient was diagnosed with squamous cell carcinoma of the distal esophagus approximately 1 year after cryoablation. This is the first complete report of squamous cell carcinoma occurring after endoscopic ablation for Barrett's neoplasia. Careful follow up is necessary in any endoscopic ablation program due to the risk of recurrent neoplasia.