(1) Background: Fragrance sensitization is common in Italy and their constituents are used in many cosmetics and detergents. The objective of the study was to analyze the temporal trend of sensitivity to fragrance mix-1 in northeastern Italy and to evaluate gender differences; (2) Methods: From 1996 to 2016, 27,381 consecutive patients with suspected allergic contact dermatitis were patch tested. Individual characteristics were collected through a standardized questionnaire in six departments of dermatology or occupational medicine; (3) Results: The overall prevalence of sensitization to fragrance mix-1 was 7.3%; the prevalence was significantly higher in women (7.7%) than in men (6.3%). From 1996 to 2016, we observed an increase of this sensitization, ranging from 6.2% to 7.7% in males and from 7.2% to 9.1% in females; (4) Conclusions: Our study showed that contact allergy to fragrance mix-1 is important in both sexes and prevalence is increasing over time, despite the introduction of new fragrances with lower sensitization potential. There is the need to reduce the use of fragrances mix-1 to stop the increase of sensitization in exposed subjects.