Colorectal cancer is the third most common cancer in the world. Despite recent therapeutic advances, it causes more than 500,000 deaths each year. The immune system plays a crucial role in protecting the body from cancer. However, cancer cells are able to evade immune detection and destruction. For example, they can downregulate antigen expression, produce immunosuppressive molecules, or recruit immune cells that perform regulatory or inhibitory functions. Understanding the complex interactions between the immune system and carcinogenesis is crucial for developing effective cancer treatments. The study aimed to determine the morphological changes in the thymus, spleen, and lymph nodes under N,N-dimethylhydrazine-induced carcinogenesis. The study was performed on 77 male outbred albino rats weighing 190-230 g, kept in standard vivarium conditions. Colon adenocarcinoma was modeled by administration of N,N-dimethylhydrazine hydrochloride for 30 weeks. To study the peculiarities of morphological and functional changes in lymphoid organs in the dynamics of colon tumor lesions, animals were withdrawn from the experiment every 30 days. Paraffin sections of the thymus, spleen, and lymph nodes 5-6 μm thick were made on a rotary microtome and stained with hematoxylin and eosin. The experimental investigation unveiled the character and extent of histological alterations within the lymphoid system organs under conditions of N,N-dimethylhydrazine-induced colon adenocarcinomatosis. As the experiment progressed, there was a noticeable escalation in the severity of detrimental and degenerative modifications observed in the thymus, spleen, and lymph nodes. These modifications were evident in the disruption of blood circulation within the examined organs, leading to vascular wall impairment and hemorrhaging, the disarray of morphofunctional elements and the development of fibrosis. Given the significant role played by the thymus, spleen, and lymph nodes in regulating carcinogenesis and maintaining immune balance, it is extremely important to delve into understanding the changes in their structure and function. Obtained results indicate that carcinogenesis is accompanied by pronounced morphological changes in the structural components of the lymphoid system organs, the degree of which increases in direct proportion to the duration of exposure to the oncogenic factor.