Nucleic acid molecules can form stable and unique motifs in DNA duplexes. Such motifs can contain tandem non-canonical base pairs and/or interdigitated base stacks, which are different from the usual single base pair mismatches in that they don't cause destabilization of the parent duplexes. Several such stable and unique motifs embedded in DNA duplexes, including the tandem sheared GA base pair, interdigitated base stacks (G/G, A/A, G/C, or A/T), and perpendicular base interaction in a drug/DNA complex, will be discussed in this report.