Purpose: This study aimed to assess the applicability of the apparent diffusion coefficient (ADC) for differentiating nasopharyngeal carcinoma (NPC) from lymphomas in the head and neck region. Material and methods: Four databases, including PubMed, the Cochrane Library, EMBASE, and Web of Science, were searched systematically to find relevant literature. The search date was updated to 8 September 2022, with no starting time restriction. The methodological quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Firstly, a random-effects model was used in a meta-analysis of continuous variables with low heterogeneity to determine the overall effect size, which was reported as the standard mean difference (SMD). Then, bivariate random effects modelling was used to calculate the combined sensitivity and specificity. The area under the curve (AUC) for each diffusion parameter was calculated after constructing summary receiver operating characteristic curves. The presence of heterogeneity was evaluated using subgroup and meta-regression analysis. Results: Twelve studies involving 181 lymphoma and 449 NPC lesions (N = 630) in the head and neck region were included, of which 5 studies provided sufficient data for pooling diagnostic test accuracy. A meta-analysis of the 12 studies using a random-effects model yielded an SMD of 1.03 (CI = 0.76-1.30; p = 0.00001), implying that NPC lesions had a significantly higher ADC value than lymphoma lesions. By pooling 5 standard DWI studies, the pooled sensitivity and specificity of ADC were 0.90 (95% CI: 0.82-0.95) and 0.63 (95% CI: 0.52-0.72), respectively. The area under the curve (AUC) calculated from the SROC curve was 0.74 (95% CI: 0.70-0.78). Conclusions: According to this systematic review and meta-analysis, nasopharyngeal carcinoma has a significantly higher ADC value than lymphomas. Furthermore, while ADC has excellent sensitivity for distinguishing these 2 types of tumours, its specificity is relatively low, yielding a moderate diagnostic performance. Further investigations with larger sample sizes are required.