Three-digit highways are related, as a rule, to the single-digit or two-digit parent US or State Road; thus State Road 205 (SR 205) is related to SR 5, and SR 120 is related to U.S. Highway 20 (US 20).

Another exception to the system was SR 265; this highway was an eighteen-mile-long (29 km) extension that existed between Interstate 265 (I-265) and I-65 and is over 100 miles (160 km) east of either SR 65 or SR 165, both located in Southwestern Indiana near Evansville.

With the completion of the Lewis and Clark Bridge Indiana 265 now exists as a part of Interstate 265.

Highways that travel through Indiana are not used as State Road numbers: these include 6, 12, 20, 24, 27, 30, 31, 33, 35, 36, 40, 41, 50, and 52.

US 6 is located similarly, and, in fact, follows the general course of former SR 6.