You have to decide how many bins you need in the histogram. For eg. the Matlab histogram function takes these forms
imhist(I) imhist(I, n) imhist(X, map)
In the first case, the number of bins is by default used as 256. So, if you have 16bit input, these will be scaled down to 8 bit and split into 256 bin histogram.
In the second one, you can specify number of bins 'n'. Lets say you specify n=2 for your 16 bit data. Then, this will essentially split the histogram as [0-2^15, 2^15-2^16-1].
The third case is where you specify the map for each bin. ie you have to specify the ranges of the pixel values for each bin.
http://www.mathworks.com/help/images/ref/imhist.html
How you want to choose the number of bins depends on your requirement.