The first successful kidney transplantation in Yugoslavia was performed in Rijeka, on the 30th of January, 1971, at that time in the “Dr. Zdravko Kučić” Hospital at Sušak, and today in the Clinical Hospital Centre (CHC) in Rijeka. The transplantation was a result of a multidisciplinary cooperation where a significant contribution was provided by the Tissue Typing Laboratory employees. Intensive preparations for the transplant procedure have been crucial for the founding of the first Tissue Typing Laboratory in Croatia as a part of the Station, later the Transfusion Medicine Institute. This paper presents the impact of the historical development of the Laboratory on the success of the transplant programme, the achievement and maintenance of the status of the CHC Rijeka, as one of the leading transplant centre in Croatia. Based on the study of the historical documents of the Laboratory and CHC archives, the development of tissue typing in Rijeka has been presented here since the establishment of the Laboratory in 1971 until the present day. The progress has been described in the adoption of new tissue typing methods in determining the polymorphism of the HLA system, the serum screening for the presence of HLA antibodies and determination of their specificity, as well as crossmatches for detecting donor-specific antibodies. Selection and application of optimal work methods at the Tissue Typing Laboratory contributed to the adoption of the latest findings in transplant immunology and the historical development of the transplant programme in Rijeka.