A near-field scanning microwave microscope (NSMM) is used to detect sequence-specific hybridization between surface-immobilized and free DNA single strands. Hybridization between target (free) and capture (immobilized) sequences leads to changes in the reflection coefficient (S11) which are measured by the NSMM. These changes are caused by hybridization-induced modification of the dielectric constant profile of the DNA film. NSMM instrumentation does not require labeling of target sequences with fluorophores or other tagging groups. The physical basis of reflection coefficient changes underpinning the NSMM approach is discussed.