Something like this perhaps (inside a mouse event: e is of type MouseEventArgs):
// get the rectangle for the first item; used for getting sideways scrolling offset
Rectangle r = listView1.GetItemRect(0);
int leftOffset = r.Left;
if (listView1.Columns[0].Width + leftOffset > e.X)
{
// first column
}
else
{
// other column
}
Update: missed that it was only the first column that was interesting; first solution picked out the column index under the mouse; this picks only the "first" or "other" cases. Note that it also takes sideways scrolling into consideration.