Aspartame is used as a nonnutritive sweetener in about 6,000 food products globally, found in Diet Coke, chewing gum, yoghurt, confections and other food products. After several decades of research on artificial sweeteners with the purpose to reduce obesity and diabetes rates, Aspartame became the most widely used from 1965 and after many toxicological and carcinogenicity studies was eventually brought to food market and approved in 1981. The USA Food and Drug Administration (FDA), legislated on the acceptable daily intake for Aspartame at 50 mg/kg (weight of human body), whereas the European Food Safety Authority (EFSA) regulatory body recommend 40 mg/kg for Aspartame for both adults and children. Food scientists and toxicologists used to question for many years if Aspartame was carcinogenic or potentially able to cause cancers during metabolism. Aspartame, after consumption it is hydrolyzed and absorbed in the gastrointestinal tract, releasing methanol, aspartic acid, and phenylalanine. All these years, several studies have investigated the carcinogenic potential of Aspartame. The vast number of in vivo (experimental animals, mice) and in vitro studies (cell isolated tissues, organs or cell cultures) indicated very low carcinogenic potential or low toxicological risks. But in the last decades some systematic studies (carcinogenicity, epidemiological) showed a positive potential of Aspartame in the development of cancer. Inevitably have led many regulatory agencies, like IARC (International Agency for Research on Cancer (WHO, Lyon, France), to reconsider the safety of aspartame for human consumption. Likewise, the results from these studies have also supported human studies, which are largely scarce. A recent French population-based study (102,000 individuals) reported an increased risk of cancer associated with Aspartame consumption. These individuals were found to be at a particularly high risk for breast cancer and obesity-related cancers including colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, ovarian, endometrial, and prostate cancers. Also, many carcinogenicity studies on Aspartame were contacted for years by the Ramazzini Institute (RI), an independent, not-for-profit research laboratory in Bologna, Italy. It initiated a series of large-scale toxicological studies in Swiss mice of the possible carcinogenicity of aspartame but the results were disputed for a long time and results were confusing. The state-of-the-art reanalysis of the Ramazzini Institute data confirms that Aspartame is a chemical carcinogen in rodents. In 2023 the International Agency for Research on Cancer (IARC, Lyon, France) decided to convene the group of international experts to decide how credible is evidence that Aspartame is carcinogenic. Inevitably, its concentration in foods and diet drinks must be reduced substantially to minimise overall risks to human health.