A positive colossal magnetoresistance (CMR) of 160% has been observed in Tb₅Si_2.2Ge_1.8 with the magnetic field applied parallel to the a axis. When the magnetic field is applied parallel to the b and c axes, the magnetoresistance (MR) is less than 8% and 5%, respectively. The CMR effect originates from intrinsic crystallographic phase coexistence. The anisotropy of the MR effect is due to a unique geometric arrangement of the interphase boundaries and large magnetocrystalline anisotropy of the compound.