Currently, Romania ranks first in Europe with regard to cervical cancer mortality. A new solution proposed for optimizing cytology-based screening, before seeing the risk associated with minor abnormalities results, is the use of molecular markers. This study concerns atypical squamous of undetermined significance (ASC-US) results, the grey zone of cytology that hides up to 15% high-grade lesions, to see how dual immunocytochemistry (ICC) staining for p16INK4a∕Ki67 help to better identify and manage high-risk (HR) ASC-US patients. We included and reviewed 183 cases with ASC-US results and p16INK4a∕Ki67 double staining (DS) performed in MICOMI Clinic (Bucharest) during 2014-2016. All patients were referred for colposcopy and biopsy if appreciated as necessary and followed-up at six and 12 months. One DS(+)∕HR human papillomavirus (HPV) negative case was positive for HPV73 Group IIB International Agency for Research on Cancer (IARC). The mean age for ASC-US in our study group was 32 years, with a median of 31 years and 31% of patients were aged 25-29 years. The sensibility of p16INK4a∕Ki67 double immunostaining was 100%, the specificity 88%, the positive predictive value (PPV) was 82%, and the negative predictive value (NPV) was 100%. The use of p16INK4a∕Ki67 ICC test optimizes the medical approach towards screening or monitoring especially in ASC-US HR HPV(+) young patients, unnecessary colposcopies are avoided thus invasive gestures at nulliparous are limited.