The construction of the Radio Chemical Hot Laboratory (RCHL) of the Joint Research Centre (JRC) of Ispra began in the early 1960s while the laboratory activities started in 1964. In 1976 an annex to the main building was built. At this time the RCHL main research activities were in environment and biochemistry by means of radioactive tracers; neutron activation analyses; extraction of actinides from radioactive liquid waste coming from the nuclear fuel reprocessing plants; and analyses of U, Pu, and Th in samples from the nuclear fuel cycle in order to determine the isotopic ratio and the burn-up. In 1978, a new area of laboratories named “Stabularium” was built to study the metabolism of heavy metal on laboratory animals. Complementary to the laboratory three pneumatic transfer systems for irradiated sources connected the RCHL to two research reactors. The decommissioning activities of the 2650 m2 facility started in January 2008 and they were completed at the end of 2010 with the release for unrestricted use of all the buildings of the facility. They consisted in five main tasks; pre-decommissioning, licensing, dismantling, waste management, and final survey. The main pre-decommissioning activities were the physical and radiological characterization of the facility. The principal licensing activity was the preparation of the delicensing documentation to obtain the license termination from the safety authorities. Dismantling consisted in the removal of all the equipments and ancillary systems, of the pneumatic transfer system, and in the decontamination of the structures of the controlled zone. The waste management was limited to the transfer of the waste and of the clearable material to the centralized waste management facility. The final survey consisted in the final radiological characterization to quantify the concentration of any residual radioactivity remained after the completion of the dismantling activities for the release of the RCHL without any radiological constraints. The safety and radioprotection prescriptions adopted were the minimization of the conventional and nuclear risk for the workers (reducing the dose rate), the minimization of the environmental risks (reducing the external liquid, solid and gaseous releases), and the confinement of the contamination where it was generated. This paper describes the pre-decommissioning, dismantling, and final survey activities undertaken to perform the decommissioning of the RCHL.