Abstract The positive clinical threshold of human papillomavirus (HPV) tests validated for primary cervical cancer screening (CCS) is designed to offer an optimal balance between clinical sensitivity and specificity. However, there may be a gap between the analytical sensitivity of the test and the positive clinical threshold, referred to here as the “gray‐zone.” This study aims to determine the prevalence and significance of HPV results obtained in the gray‐zone in routine practice. Cervical samples obtained in our institution for CCS over a 22‐month‐period were tested with the Alinity m HR‐HPV Assay (Abbott). Clinical and biological data, including cytological results and patients' HPV history were collected. Of the 6101 samples collected, 1.7% had an HPV result in the gray‐zone (102 patients). The proportion of gray‐zone results varied according to HPV genotype, reaching 11.8% of samples with detectable HPV DNA in the case of HPV31/33/52/58 genotypes. Reflex cytologies showed no abnormalities or Atypical Squamous Cells of Undetermined Significance results in 74.6% and 17.9% of cases, respectively. A previous or subsequent HPV‐positive result with a (possibly) identical genotype was observed in 58% and 38% of cases, respectively. Two women with a history of persistent HPV detection had a CIN2+ lesion 1 year after the gray‐zone result. In conclusion, the proportion of HPV results in the gray‐zone varies according to genotype. No cytological abnormality is observed in the majority of cases, but a few rare patients with a history of persistent HPV infection should be closely monitored even if the HPV result is transiently located in the gray‐zone.