The synthesis of and magneto-transport in the "colossal magnetoresistance" (CMR) pyrochlore-structure compounds Tl2-xScxMn2O7 for 0 less than or equal to less than or equal to 0.5 are reported. The maximum resistivity (rho) increases by 10(5) while the Curie temperature (T-c) decreases by only 25% between x = 0 and 0.4. For x = 0.2 to 0.3, the magnetoresistance at both high field (6 tesla) and low field (<0.05 tesla) are significantly enhanced over the undoped (x = 0) compound. Structural analysis indicates that all of the manganese ions are near the +4 oxidation state. The behavior of rho and T-c suggests that scandium substitution affects mainly electronic conduction on the thallium-oxygen sublattice while leaving the magnetism essentially unchanged. These results demonstrate a distinct way of manipulating magneto-transport properties in CMR materials.