Dear Mister Jones

Generally speaking, the answer is yes.  If you ommit the comma, it can lead to ambiguous meanings.  Following is an example.

• I would like to thank my parents, Sandy and God.

In this sentence, is the person thankful for his parents, who are Sandy and God??? Or is he thankful for 4 people, his parents, Sandy, and God?

If you insert the comma before the ‘and’ (this comma is called the serial or Oxford comma, by the way), then your meaning will be clearer:

• I would like to thank my parents, Sandy, and God.

However, what if you wanted to say the following:

• I would like to thank my mother, Sandy, and John.

Now, regardless of whether you use a comma after ‘Sandy’ or not, the meaning could still be ambiguous.  Is Sandy the mother or is she a different person?  When confronted with this sort of a list of three or more elements, the trick is to order them in a way that removes any ambiguity.  Or, you can use different punctuation to make the meaning clearer.

Let’s look at some ways we can reorder this to make our meaning clear:

• I would like to thank John, my mother, and Sandy. (3 distinct people, assuming John is not your mother’s name)
• I would like to thank my mother (Sandy) and John.  (2 distinct people)
• I would like to thank my mother and Sandy and John.  (3 distinct people)

When it comes to lists of the x, y, and z fashion - I always prefer to include the comma before the ‘and’.  However, even that won’t always remove ambiguity - so then you must find ways to change the sentence so that your meaning is clear.