The classic association between cancer and mitochondrial dysfunction is actually considered as a role of mitochondria in cellular signalling. It is understood that mitochondria, mitochondrial oxidative damage and NO and H2O2 diffusion are involved in the progression of human colorectal cancer. Mitochondria from human colorectal tumors and adjacent non-tumor colon tissues showed a markedly increased oxidative damage with increased contents of TBARS and protein carbonyls. Mitochondrial protein carbonyls was the most sensitive indicator. Oxidative stress and damage was also observed in adjacent non-tumor cells. Mitochondrial activities, as NADH-cytochrome c reductase and cytochrome oxidase, were observed decreased in tumor and in adjacent non-tumor tissue. Cu,Zn-SOD activity decreased by 42% in tumor tissue in the advanced stage as compared with the initial stage, whereas Mn-SOD activity did not change in tumor progression. An increased mtNOS activity (46%) was observed in tumor and non-tumor tissues in the advanced stage of cancer progression. A direct linear relationship between mtNOS and oxidative damage in tumor and non-tumor tissues supports the concept that mitochondrial NO and H2O2 diffuse from tumor to adjacent non tumor tissue signaling for cell death as the classic toxohormones.