There is a lack of predictive biomarkers that can identify patients with head and neck squamous cell carcinoma (HNSCC) who will experience treatment failure and develop drug resistance, recurrence, and metastases. Cancer stem-like cells (CSC) were identified as a subset of cells within the tumor in a variety of solid tumors including HNSCC. CSC are considered the tumor-initiating population responsible for recurrence or metastasis and are associated with therapy resistance. This meta-analysis including fourteen studies with altogether 1258 patients updates and summarizes all relevant data on the impact of ALDH1+ CSC on the prognosis of HNSCC and its association with clinicopathological parameters. ALDH1 expression is highly correlated with tumor differentiation (G3 vs. G1+G2; odds ratio = 2.85. 95% CI: 1.72-4.73, P<0.0001) and decreased overall survival (relative risk = 1.77. 95% CI: 1.41-2.22, P<0.0001) if one out of seven studies was excluded because of heterogeneity. These findings provide insights into the understanding of more aggressive tumor phenotypes and also suggest that the prognostic value provided by HNSCC-subtyping by CSC frequency warrant further clinical investigation.