Background: In the present MPOX outbreak, differences related to clinical and epidemiological features have been observed with respect to historical evidence. In Chile, the first case was reported in June and until now, there are more than 1400 cases. Objective: To identify differences between confirmed and discarded cases of MPOX during 2022 Chilean outbreak. Methods: This is a retrospective case-control study from the Institute of Public Health database from all suspected cases between June 1st and September 30th of 2022. Patient samples were processed by real-time PCR at the same Institute. RStudio and Microsoft Excel were used for statistical analysis. Means, frequencies and percentages were calculated. Fisher's test was used to compare groups. Results: We collected 1456 suspected cases. 87% were men between 30-39 years. Positivity increased from 20% at the start to 73% at the peak. 100% had exanthema. The proportion of lymphadenopathy (31% vs 12%), fever (42% vs 29%), myalgia (35% vs 25%), and type of lesion: pustule (36% vs 27%), scab (25% vs 17%) and umbilicated lesion (24% vs 7%) was mayor in positive than negative case (p <0.05). In the confirmed cases, the most frequent site of lesion was genital and anal area, 48% had multiple sexual partners and 14% having had contact with a positive case. 41% have a history of sexually transmitted diseases (HIV=39%). Conclusions: Main differences between confirmed and discarded cases were lesion features and distribution. Principal risk factors were previous contact with another positive case and multiple sexual partners. The current case definition seeks to be highly sensitive to capture the largest number of cases, being strategic at the beginning to detect an outbreak. We postulate that, for sustained epidemiological surveillance, a more specific definition in accordance with findings of current outbreak could be formulated.