Background: To estimate the transition probabilities of esophageal cancer (EC) and its precancerous lesions during the process of canceration by Markov model, which could provide important information for EC screening with regard to choosing reasonable screening and follow-up intervals.Methods: The transition probabilities among pathological stages were estimated by establishing Markov models for the natural history of EC and repeatedly adjusting and calibrating Markov models through comparing the modeled incidence and distributions of pathological stages (alone or combined) with observed data in real world condition. Results: In one year, the probabilities were 0.024, 0.05, 0.12 for people from health state progressing to mild dysplasia (mD), mild dysplasia (mD) to moderate dysplasia (MD), and moderate dysplasia (MD) to severe dysplasia/carcinoma in situ (SD/CIS), respectively. The age-specific transition probabilities were 0.08~0.18 for severe dysplasia/carcinoma in situ (SD/CIS) progressing to intramucosal carcinoma(IC), 0.4~0.87 for intramucosal carcinoma (IC) to submucosal carcinoma (T1N0M0) (SC), and 0.2~0.85 for submucosal carcinoma (T1N0M0) (SC) to invasive carcinoma (INC). The progression probabilities increased with age and the severity of the disease. Based on the estimated transition probabilities, we predicted the incidence of EC and distributions of its pathological stages. Comparisons between modeled results with observed data confirmed the validation of our transition probabilities.Conclusion: The estimating transition probabilities of EC and its precancerous lesions were reliable and could be used to address questions such as the optimal screening frequency, screening intervals, and health economic evaluation of screening strategies.