It's possible, yes, but you would need to use multiple selectors, checking the that first cell was also the 4th last cell, the 2nd also the 3rd last, and so on:
.myclass2{
background:#000;
color:#fff;
}
td:first-child:nth-last-child(4)>.myclass2,
td:nth-child(2):nth-last-child(3)>.myclass2,
td:nth-child(3):nth-last-child(2)>.myclass2,
td:nth-child(4):last-child>.myclass2{
background:#f00;
}
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
</tr>
</table>
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
<td>4 <span class="myclass2">xxx</span></td>
</tr>
</table>
Or, alternatively, just select the first child that is also the fourth last child and any cells that follow it:
.myclass2{
background:#000;
color:#fff;
}
td:first-child:nth-last-child(4)>.myclass2,
td:first-child:nth-last-child(4)~td>.myclass2{
background:#f00;
}
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
</tr>
</table>
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
<td>4 <span class="myclass2">xxx</span></td>
</tr>
</table>
Another way to do it, if you wanted to target rows with any number of cells greater than 3 would be to use the negation pseudo-class to select the first cell that isn't the last, 2nd last or 3rd last cell and all cells that follow it:
.myclass2{
background:#000;
color:#fff;
}
td:first-child:not(:nth-last-child(-n+3))>.myclass2,
td:first-child:not(:nth-last-child(-n+3))~td>.myclass2{
background:#f00;
}
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
</tr>
</table>
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
<td>4 <span class="myclass2">xxx</span></td>
</tr>
</table>
<table class="myclass">
<tr>
<td>1 <span class="myclass2">xxx</span></td>
<td>2 <span class="myclass2">xxx</span></td>
<td>3 <span class="myclass2">xxx</span></td>
<td>4 <span class="myclass2">xxx</span></td>
<td>5 <span class="myclass2">xxx</span></td>
<td>6 <span class="myclass2">xxx</span></td>
</tr>
</table>
NOTE: These may not be optimal solutions for you, given the poor support some e-mail clients have for CSS.