Genomic sequences for many animal species are now available in the public domain. Protein similarity search in evolutionarily distant organisms by sequence comparison often turns out to be difficult. Here, we present the Structure and Sequence Alignment (SnS-Align) tool that graphically presents pairwise local alignment of sandwiched protein sequences, a hybrid of the primary protein sequence and its secondary structure. The utility of the tool is demonstrated by sample analysis of the gap junction protein superfamily of innexins/pannexins and the classic myoglobin family. SnS-Align can also be used for demarcation of the structurally conserved domains within superfamilies of paralogous genes.