The oncoprotein Tax was characterized genetically from a large cohort of human T-cell lymphotropic virus type 1 (HTLV-1) seropositive individuals from the most endemic region of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 infection in Argentina, the province of San Salvador de Jujuy. Sixteen HAM/TSP patients and 47 HTLV-1 healthy carriers were evaluated. Six Tax genetic polymorphisms were identified and observed in 70.8% of healthy carriers and 62.5% of HAM/TSP patients. Tax genetic polymorphisms were not associated with clinical status but A8344C polymorphism statistically provide a borderline protective effect of HAM/TSP outcome. Nucleotide diversity in healthy carriers was 0.00549, whereas HAM/TSP virus population revealed a low diversity of 0.00379, suggests a positive selection for Tax protein conservation in this group. It is concluded that tax genetic polymorphisms do not increase the risk of developing HAM/TSP in this endemic region. However, in spite of the low prevalence of HTLV-1aB genotype, statistical analysis revealed an important correlation of tax genetic signatures with HTLV-1aA trans-continental subgroup.