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Lugol-voiding lesions (LVLs), detected by chromoendoscopy using iodine dye in patients with esophageal squamous cell carcinoma (EC) or head and neck squamous cell carcinoma (HNC), are associated with a second primary carcinoma in the other organ. We undertook a cross-sectional and retrospective cohort study to assess the risk for second primary carcinomas according to the severity of LVLs, on the basis of their number and size.A total of 1,060 patients with only EC, only HNC, or both EC and HNC (EC+HNC) underwent esophageal endoscopic examination between January 1994 and January 2010. The patients were classified according to the number of LVLs in an endoscopic visual field and the size of the largest LVLs. Factors associated with the second primary EC or HNC were analyzed.Univariate analysis showed that a larger number and size of LVLs increased the risk for synchronous and early metachronous second primary cancer (Pvalue for trend <0.0001). Multivariate analysis showed that a number of LVLs ≥20 (EC+HNC vs. only HNC, odds ratio (OR)=15.7; EC+HNC vs. only EC, 3.5) and a size ≥10 mm (EC+HNC vs. only HNC, OR=3.1; EC+HNC vs. only EC, 3.2) were independent risk factors for synchronous and early metachronous second primary cancer. A larger number of LVLs was a risk factor for metachronous EC and HNC, and a size ≥10 mm was a risk factor for late metachronous EC.The severity of LVLs in patients with HNC or EC closely correlated with a second primary carcinoma in the other organ. Patients with LVLs must be followed closely for development of a second primary carcinoma.