Objective To evaluate the clinicopathologic features, prognostic factors, and management of patients in the North Chinese population with head and neck squamous cell carcinoma (HNSCC) who developed a second primary malignancy (SPM). Methods This was a retrospective study including 1818 eligible patients between June 1999 and April 2011. Results A total of 188 HNSCC patients developed SPM. Multiple oral dysplastic lesions (MODLs) ( P  < .001) were among the risk factors for occurrence of SPM. However, MODLs were closely associated with many mild pathologic features, such as early T stage ( P  < .001), early N stage ( P  = .036), good pathologic differentiation ( P  < .001), and mild growth pattern ( P  < .001). Interestingly, multivariate survival analysis showed that SPM patients had a better prognosis if they had the characteristics of MODLs ( P  = .020). Conclusions MODLs were a crucial risk factor leading to the occurrence of oral SPM after an index HNSCC in patients in Northern China. However, SPM patients with the characteristics of MODLs had a better prognosis.