Many variants of the DR3/LARD death receptor mRNA are derived during alternative splicing. Different DR3/LARD mRNAs encode the membrane and soluble forms of the receptor, which perform different functions. The frequency of the spliced mRNA variants of DR3/LARD was assessed by RT-PCR in patients with colorectal cancer and in cancer cell lines. Four forms of the DR3/LARD death receptor mRNA were detected with different frequencies in the studied samples. Two of them encoded the membrane molecules (LARD 1a mRNA and DR3 mRNA) and two other forms expressed the soluble forms of the receptor (LARD 3 mRNA and soluble DR3 mRNA). In the blood of healthy volunteers, 11 variants (spectra) of DR3/LARD mRNA forms were identified, and the full spectrum that included all four variants of DR3/LARD mRNA dominated. In blood and tumor center samples from patients with colon cancer, six spectra of DR3/LARD mRNA were found. The diversity of the DR3/LARD mRNA spectra was decreased in colon cancer patients due to the reduced frequency of soluble DR3 mRNA. In samples of tumor centers, the spectrum with the absence of only mRNA of the soluble DR3 form dominated. In the blood of patients, two spectra prevailed, i.e., the full spectrum and LARD 1a mRNA and LARD 3 mRNA. Only these two spectra of DR3/LARD mRNA were also found in cancer cell lines. Distinctions in the frequency of DR3/LARD mRNA spectra in healthy volunteers and patients with colorectal cancer can define the different susceptibility of immunocompetent and tumor cells to apoptosis signals.