In February 2016, Santé publique France was contacted by a research laboratory located in the Île-de-France region regarding five cases of kidney cancer that occurred among employees between 2012 and 2015. A spatio-temporal cluster investigation in the workplace was conducted. The objective was to verify whether there was an excess incidence of kidney cancer cases among the laboratory’s active employees, as well as their exposure to one or more plausible risk factors associated with this disease. Ultimately, the investigation, conducted over an 11-year period from 2006 to 2017, did not reveal an excess of kidney cancer cases among the laboratory’s employees compared to what would be expected given the disease’s prevalence. Nor was any common exposure identified among all cases, nor was any chemical, biological, or physical agent recognized as a kidney carcinogen found to have regularly exposed the identified cases. This approach, however, has limitations: it did not include employees hired as subcontractors or employees who had retired in the absence of medical information regarding them. Nevertheless, the absence of an observed excess incidence of kidney cancer among employees of the research laboratory supports the conclusion that the signal reported in 2016 is unfounded. Finally, the specific exposures reported during the investigation highlight the importance of continuing the risk prevention measures already in place within the laboratory by including contractors and interns, as well as continuing exposure monitoring through individual follow-up of employees by occupational health services. Based on these results, there are no objective reasons to extend the investigations into this signal, unless new cases of kidney cancer are reported among the laboratory’s workforce. The enhanced surveillance already implemented by occupational health services—which prompted this signal—must be maintained to enable the earliest possible detection of new cases.