In Madison County, NY 12B directly abuts the campus of Colgate University in the village of Hamilton.

A mix of residences and businesses parallel NY 12B, which leaves the village for the town of Sherburne to the northwest.

[3] After Earlville, NY 12B continues northward into the town of Hamilton, where it becomes a two-lane rural highway once again.

Leaving Oriskany Falls, NY 12B loses the North Main moniker and becomes a two-lane rural road through a quarry in the town of Marshall.

[3] In Marshall, NY 12B bends to the northeast and away from the quarry, remaining a two-lane road of fields and residences.

After a mobile home, NY 12B begins to straighten to the north, entering the hamlet of Marshall, where it becomes a two-lane commercial roadway.

At this junction, NY 12B turns northward on East Park Row, before leaving downtown Clinton to the northeast via Utica Street.

A short distance after crossing into the town of New Hartford, NY 5B turns northward onto Middle Settlement Road.

[6] The portion of NY 12 between Sherburne and Utica was realigned in 1928 to follow a new, more direct alignment to the east.

According to a study by the New York State Department of Transportation (NYSDOT), 93 accidents occurred along this portion of NY 12B from November 2006 to October 2009.

Of those, 50 were the result of striking an animal while 15 others were cases where a motorist crashed into a fixed object.